(3) Systematic errors may arise when using circulating cytokines: for example, Roerink et al. have reported that most cytokines remain in the intercellular environment, where actual cytokine levels (particularly those of IL-1) are generally below the threshold of detection [60], but in a later study of the same authors found that the normalized protein expression value of IL-12p40 and CSF-1 was significantly higher in patients with CFS [61]. This evidence concerns the gene IL1A and myalgic encephalomeyelitis/chronic fatigue syndrome.